Recent progress using adoptive T cell-based therapy with chimeric antigen receptors (CAR) shows impressive successes in patients with cancer by enhancing the effectiveness of CAR T cells. A major gap in the current knowledge is having an easy way to predict the effectiveness of CAR T cells. Specifically, many scientists from different laboratories are generating different CARs with minor modifications. However, before these modified CARs can enter clinical trials, it is essential that they be evaluated accurately for their quality, safety and potential effectiveness, in a cost-effective manner. The conventional tools for immunological analyses of quality and effectiveness are time-consuming, labor intensive, costly, and inaccurate.
The immunological synapse (IS) was originally described by imaging T-cell interactions with antigen-presenting cells (APCs). The structure, function, and signaling cascades at the synapses have been further confirmed by imaging of T-cell interactions with the glass-supported planar lipid bilayer containing the MHC-peptide complex and other co-stimulatory molecules. The general consensus in the field of immunology is that the glass-supported planar lipid bilayer system can be used for mimicking the target cells to study synapses at high resolution. Although tremendous progress has been made in the basic research on the IS, with a focus on the structure, function, and signaling cascades, to date no study has addressed how the synapse of the CAR controls CAR T cell activation.
The present disclosure provides a solution to a long-felt need in the art how to measure the efficacy of therapeutic immune cells, including CAR T cells.